Week 2 Flashcards
1
Q
RNA structure
A
Single stranded, ribonucleotides, more unstable than DNA, contains U (not T)
2
Q
rRNA
A
Core of ribosome, catalyzes protein synthesis
3
Q
tRNA
A
Form adaptors that select/hold onto AAs during protein synthesis
4
Q
mRNA
A
Short lived, coding RNAs in protein synthesis
5
Q
snRNA
A
direct splicing of pre-mRNA to mRNA (remove introns)
6
Q
siRNA
A
Regulate eukaryotic gene expression by degrading select mRNA (typical in lab setting)
7
Q
miRNA
A
Regulate gene expression by blocking translation of select mRNA (more biologically relevant)
8
Q
RNA Polymerase I
A
Makes rRNA
9
Q
RNA Polymerase II
A
Makes mRNA
10
Q
RNA Polymerase III
A
Makes tRNA
11
Q
Coding strand of gene
A
Non-template strand identical to RNA sequence produced
12
Q
Transcription start site
A
+1 position, usually has A or G; basal transcription factors and RNA polymerase bind here
13
Q
Transcription stop site
A
Contains poly A tail which is clipped off during RNA processing
14
Q
Transcription unit
A
Linear sequence of DNA from start to stop site
15
Q
Promoter
A
Sequence upstream of start site where basal transcription factors bind, recruit RNA polymerase
Ex: TATA, CAAT
16
Q
Enhancer/Silencer
A
Short sequences that influence rate of transcription
17
Q
General Transcription Factors
A
Initiate transcription, form protein-DNA /protein-protein complexes on promoter; position RNA polymerase, pull apart DNA strands, release RNA polymerase
18
Q
Initiation of transcription
A
- TFIID binds to TATA box, recruits TFIIF/RNA Pol II/TFIIE, TFIIH to form initiation complex
- DNA strands separate via TFIIH to expose DNA template strand
- Polymerization of short lengths of RNA
19
Q
TFIID
A
Binds to the TATA box during initiation via TBP subunit
20
Q
TFIIH
A
Unwinds DNA double helix to expose DNA template during initiation
21
Q
7-methyl-guanosine cap
A
Modification to the 5’ end of mRNA that protects against degradation, helps bind mRNA to ribosome during translation
22
Q
Histone acetyl transferase (HAT)
A
Acetylates histones to reduce positive charge, loosen interaction with DNA
23
Q
Histone deacetylases (HDACs)
A
Remove Acetyl group and reverse HAT action
24
Q
Elongation of transcription
A
RNA Pol II phosphorylated by TFIIH, polymerase leaves promoter and elongation begins - RNA Pol moves stepwise along DNA and unwinds helix
25
DNA gyrase
Relieves superhelical tension during elongation
26
Termination of transcription
RNA Pol encounters termination signals on DNA template - string of AT nucleotide pairs preceded by 2-fold symmetric DNA sequence
27
Self complementary hairpin structure of RNA
Destabilizes interaction between RNA/RNA Pol
28
mRNA processing
Includes 7-methyl-guanosine cap, splicing, and polyadenylation at 3' end
29
How transcription is regulated
Several regulatory proteins bind to DNA to control activity (homeodomain, zinc finger, leu zipper HLH proteins)
30
Relationship of TFs and cancer
Mutated genes for transcription factors may lead to oncogenes
31
FMR1 gene
Encodes for protein with neurological function; excess number of CGG repeats leads to suscecptibility of cytosine methylation - gene will be silenced/transcription turned off
32
Start codon
AUG/Met/M
33
Stop codons
UAA/UAG/UGA
34
Silent mutation
Does not change the AA
35
Missense mutation
Changes AA in protein with either no effect on function or vastly different function
36
Nonsense mutation
Codon changes to a STOP codon causing premature chain termination; degradation or truncated version of protein
37
Frameshift mutation
Most serious; one or more nucleotides deleted or inserted into ORF - change in codon sequence/alteration of AA sequence
38
Anticodon loop of tRNA
Set of 3 consecutive nucleotides that pair with complementary codon in mRNA molecule
39
3' CCA terminal region
Binds amino acid that matches the corresponding codon
40
Wobble hypothesis
tRNAs require accurate base pairing only at the first 2 positions of the codon and can tolerate a mismatch at the 3rd position; explains why alternative codons for an AA only differ in 3rd nucleotide
41
Aminoacyl tRNAs
"Activated" AAs; catalyzed by Aminoacyl synthetase
42
Transcription Factors (general role)
Bind to promoter/enhancer to activate/repress transcription; interact with RNA polymerase II
43
Hox Genes
Repetitive DNA regulators that influence axial development; main regulator of Hox genes = RA
44
Pax Genes
Formation of tissues/organs
45
Aniridia
Eye disorder-absence of iris; mutation in PAX6
46
Lim Proteins
Formation of body segments
47
Dlx Genes
Patterning of outgrowing appendages, jaws, inner ear
48
Msx Genes
Prenatal inhibitor of cell differentiation; postnatal proliferative capacity of tissues
49
Tbx Genes
Mesodermal germ layer development (specifies forelimb and hindlimb)
50
Basic Helix-Loop-Helix Transcription Factors
Regulate myogenesis
51
FOXP2
Associated with disorders of speech/language development; human specific; HLH family
52
Campomelic dyspasia
Mutations near SOX9; effects skeletal, reproductive, respiratory systems (Sox9 = Zn finger family)
53
WT1 gene
Wilms tumor suppressor gene; kidney and gonadal development (Zn finger protein)
54
Hedgehog proteins
Use ligand receptor complex; NOT a TF
55
Hedgehogs and Wnts
protein SIGNALS
56
Hox, Pax, Msx, Lim,etc
Transcriptional regulators/TFs
57
Wnt signaling
Transduced to b-catenin which affects transcription (cancer if not regulated)
58
RAS
Proto-oncogene; if mutated will be perpetually active, occurs in 25% of all cancers
59
HER2
Proto-oncogene; Resulting oncoprotein is NEU observed in some breast cancers
60
EGF receptor
Proto-oncogene; Resulting oncoprotein observed in glioblastoma
61
N-MYC
Proto-oncogene; observed in neuroblastoma
62
c-MYC
Proto-oncogene; Observed in Burkitt lymphoma
63
ABL
Proto-oncogene; observed in CML
64
p53
Tumor suppressor; monitors cell cycle checkpoints; observed in 50% human tumors
65
RB
Tumor suppressor; Regulates G1 phase; observed in retinoblastoma
66
APC
Tumor suppressor; Regulates cell proliferation; observed in FAP (precursor of colon cancer)
67
DCC
Tumor suppressor; Involved in cell proliferation, migration, apoptosis; observed in colon cancer
68
BRCA1/BRCA2
Tumor suppressor; Involved in DNA repair and apoptosis; observed in breast cancer
69
NF-1
Tumor suppressor; involved in GAP formation; observed in neurofibromatosis
70
Epitope
Region of antigen binding to Fab fragment of antibody
71
Indirect ELISA
Ag coated well with specific Ab added, then enzyme-linked Ab added, then substrate converts enzyme to colored product; Color indicates amount of Ab to specific Ag
72
Sandwich ELISA
Ab coated well; Ag binds to Ab; 2nd enzyme linked Ab added and substrate converts to colored product; Color indicates quantity of antigen
73
PCR
Separate DNA strands, anneal primers, synthesize DNA; main purpose if AMPLIFICATION for identification of altered genes or foreign DNA
74
PCR analysis of Huntington's
Many more repeats seen in PCR vs in healthy individual
75
STRs
Forensic application; varying repetitive regions of DNA sequences that identify individuals
76
Microarrays
Fluorescently marked DNA injected onto chip; scanned, intensity of signal demonstrates gene expression
77
Pregnancy dating
LMP clinically used - fertilization plus 2 weeks
78
Fertilization
Occurs in ampulla (distal 2/3 of fallopian tube); results in completion of 2nd meiotic division, restoration of diploid number of chromosomes, metabolic activation of oocyte, initiation of cleavage
79
Capacitation
Glycoprotein coat and seminal plasma proteins removed from plasma membrane of sperm
80
Hyaluronidase
Enzyme that disperses corona radiata for passage of sperm
81
Zona reaction
block to polyspermy
82
Cleavage
Occurs 30 hours after fertilization; increase in cell number with decrease in cell size; morula development
83
Blastocyst
Assembled during days 5-7 of development; contains blastocyst cavity, inner cell mass, and trophoblast
84
Trophoblast
Releases early pregnancy factor (immunosuppressant), supportive cells that line entire blastocyst
85
Inner cell mass
Differentiates into epiblast and hypoblast
86
Cytotrophoblast
Contains mitotically active stem cells, form placenta
87
Syncytiotrophoblast
Contains proteolytic enzymes, secretes hCG (implantation signal)
88
Epiblast
Differentiates into amnion, amnionic cavity, ectoderm (ICM derivative)
89
Hypoblast
Differentiates into extraembryonic tissue for signaling (ICM derivative)
90
Extraembryonic somatic mesoderm
Lines trophoblast, covers amnion
91
Extraembryonic splanchnic mesoderm
Lines the yolk sac
92
Derivatives of extraembryonic mesoderm
Connecting stalk, primitive blood, chorion
93
Hydatidiform Mole
Abnormal trophoblastic proliferation; complete results from fertilization of empty oocyte, partial results from fertilization of a normal oocyte by 2 sperm
Clinical: vaginal bleeding, pelvic pain, enlarged uterus, morning sickness
94
Choriocarcinomas
Malignant tumor developed from hydatidiform mole
95
Ectopic pregnancies
Most occur in uterine tubes; diagnosed by ultrasound; s/s cramping and pain; due to smoking, PID
96
Placenta previa
Implantation too close to the cervix; key feature: vaginal bleeding beyond 20 weeks gestation; risk of hemorrhage
97
Gastrulation
Formation of 3 germ layers (ectoderm, mesoderm, endoderm)
98
Ectoderm derivatives
skin, hair, nails, CNS
99
Mesoderm derivatives
muscle, bone, blood, heart, connective tissues
100
Endoderm derivatives
lungs, GI, bladder
101
Primitive streak
Forms in epiblast, contains primitive groove where ectoderm involutes
102
Teratoma
May be remnant of primitive streak or inappropriately migrated germ cells; mixture of many tissues; can be sacrococcygeal or oropharyngeal
103
Notochord
Extends from primitive node anterior to prechordal plate; serves as template for vertebral column; induces neural plate
104
Chordomas
Rare aggressive neoplasms of bone; arise from remnants of notochord
105
Paraxial mesoderm
Forms somites (myotome, sclerotome, dermatome)
106
Intermediate mesoderm
Forms urogenital system (kidneys, gonads)
107
Lateral plate mesoderm
Forms connective tissue (blood, lymph, mesenteries, cardiovascular)
108
Cell cycle stages
G1, S, G2, M
109
G1 phase
RNA, protein synthesis; cell growth; Restriction and G1 checkpoints
110
S phase
DNA replication, histone synthesis, centrosome formed, chromosome duplication
111
G2 phase
Prepraration for mitosis, ensuring DNA stability; G2 checkpoint
112
M phase
Mitosis; Metaphase checkpoint
113
Restriction point
Passage requires growth factor independence; limited growth factors lead to cell cycle arrest in G1 phase
114
G1 checkpoint
Corrects DNA damage (chemical modifications) before continuing to S phase
115
G2 checkpoint
Verify completeness of complete genomic duplication
116
Metaphase checkpoint
Ensures chromosomes are attached to mitotic spindle
117
Cyclin-CDK complex
Cause changes in phosphorylation of substrates that regulate cell cycle events (cyclins regulate Cdks)
118
CAK
Fully activate Cyclin-Cdk complex
119
WEE1 kinase
Phosphorylates roof site of Cyclin-Cdk complex to inactivate it
120
Cdc25 phosphatase
De-phosphorylates roof site of Cyclin-Cdk to activate it
121
p27
CKI-Physical interaction with Cyclin-Cdk complex inactivates it
122
In which phase does Cyclin D complex with CDKs 4,6?
G1
123
In which phase does Cyclin E complex with CDK2?
G1-S transition
124
In which phase does Cyclin A complex with CDK2?
S
125
In which phase does Cyclin A,B complex with CDK1?
Mitosis
126
APC/C
Activated by Cdc20; ubiquitination of M-cyclin or S-cyclin so CDK inactivated
127
Extrinsic apoptotic pathway
Triggered by external stimuli; involves Fas ligand binding to Fas death receptor, FADD, and intiator caspase 8
128
Intrinsic apoptotic pathway
Triggered by internal stimuli; MITOCHONDRIAL dependent; release of cytochrome c from mitochondria leads to Apaf1, apoptosome which causes activation of initiator caspase 9
129
Caspase 3
Executioner caspase, can be activated by extrinsic (caspase 8) or intrinsic (caspase 9) pathways
130
BAX (BH123) protein in apoptosis
Activated and aggregate to induce release of cytochrome c from mitochondria
131
BCL2 protein in apoptosis
Anti-apoptotic protein that inhibits BAX pathways
132
Autosomal dominant disorders
Only 1 allele needed for expression; M/F can transfer to M/F; recurrent risk of affected children = 50%; vertical transmission in pedigrees
133
Autosomal recessive disorders
2 copies of allele needed to influence phenotype; 25% chance of inheritance; 50% chance of becoming a carrier
134
X-linked recessive disorders
Female carriers transmit the gene; no male carriers
135
X-linked dominant disorders
RARE; no carriers; Males only transmit to females
136
Reduced penetrance
Frequency that a gene manifests itself; suggest multifactorial aspects of disease
137
Variable expressivity
Range of phenotypes that vary between individuals with a specici genotype
138
Locus heterogeneity
Single disorder/trait/pattern of traits caused by mutations in genes at different chromosomal loci
139
Pleiotropy
Single gene produces two or more effects
140
When does crossing over occur
Prophase I of meiosis
141
Genomic imprinting
Methylated genes are silenced/down regulated; ex: Prader Willi, Angelman syndromes
142
Nondisjunction
Homologs fail to properly separate; increases with maternal age
143
Aneuploid
Abnormal chromosome number (such as trisomy)
144
Genotype frequency
Number of desired genotype divided by total number of genotypes
145
Allele/gene frequency
Number of desired alleles divided by total number of alleles present
146
Hardy-Weinberg Principle
Determines population frequencies of genotypes;
| AA=p2, Aa=2pq, aa=q2; p+q=1
147
Polygenic traits
Variation thought to be caused by combined effects of multiple genes
148
Multifactorial traits
Environmental factors cause variation in trait
149
Heterochromatin
Dark staining, genetically inactive; highly condensed; genes will be silenced if relocated near heterochromatin
150
Euchromatin
More loosely packed, lighter stained, transcriptionally active
151
Effect of histone acetylation on DNA
Loosens interaction between histones and DNA; neutralizes positive charge and promotes transcription
152
Effect of salt linkages on DNA
Neutralize negative charged DNA backbone
153
Effect of histone methylation on DNA
Keeps histone/DNA interaction loose and promotes transcription
154
Nucleosomes
"Beads on a string" configuration, basic unit of chromosome packing
155
CGH Arrays
Detects copy number variation by comparing human DNA on chip to reference DNA strand
156
Asymmetry of DNA replication fork
Leading strand synthesized continuously, Lagging strand synthesized in segments
157
DNA Helicase
Unwinds DNA via ATP hydrolysis to separate strands
158
Topoisomerase
Relieves supercoiling of DNA strand (Type I works on one DNA strand, Type II works on both strands)
159
DNA Polymerase
Synthesizes RNA from DNA template and has proofreading capability
160
Single-stranded binding proteins
Binds ssDNA that has been separated to stabilize DNA and prevent formation of hairpins
161
DNA Ligase
Seals nicks in DNA
162
Spontaneous DNA damage
Depurination (whole purine gone), Deamination (C to U); if unrepaired lead to deletion or BP substitution
163
DNA damage due to UV radiation
Pyrimidine dimers - stacking of pyrimidines that lead to toxic products
164
Ionizing vs. Non-ionizing DNA damage
Ionizing does enough damage to misplace electrons from atoms (due to X-rays, CT scans); Non-ionizing does not (UV radiation)
165
Methylated cytosines
Produces T mismatched with G bases; repair is ineffective; associated with inactive genes
166
Direct repair
Photolyase repairs pyrimidine dimers
167
Base Excision Repair
DNA glycosylase recognizes altered base and catalyzes removal; DNA polymerase adds nucleotide and DNA ligase seals nicks
168
Nucleotide Excision Repair
Repairs bulky lesion such as thymine dimers; NER complex scans DNA for distortion, cleaves backbone; helicase pulls away lesion, DNA polymerase and ligase repair gap
169
Xeroderma pigmentosum
Severe inherited light sensitivity; due to unrepaired thymine dimers; defective XP proteins in NER complex fail to repair DNA
170
Cockayne's syndrome
Due to defect in transcription coupled repair; RNA polymerase permanently stalled at damaged site
171
Transcription coupled repair
RNA polymerase stalls at damaged site and signals repair machinery; specific for strand being transcribed
172
Double stranded break repair
Non-homologous end joining brings broken strands together via DNA ligation; some nucleotides lost
173
Mismatch repair
Removes distortions in DNA via MER complex, DNA polymerase and ligase
174
Hereditary colon cancer
Inherited mutation in MER complex; increased susceptibility-tumor will form if good gene acquires a mutation
175
Acceptor (A) site
Where mRNA codon exposed to receive aminoacyl tRNA (except Met)
176
Peptidyl (P) site
Where aminoacyl tRNA attached
177
Empty (E) site
Location occupied by empty tRNA before exiting ribosome
178
Inititiation (Translation)
(Met) Initiator tRNA binds to P site of small SU; interacts with mRNA until it finds AUG; large SU added and translation begins
179
Elongation (Translation)
Ribosome extends polypeptide chain by loading aminoacyl tRNA that base pairs with A site codon; elongation factors involved for efficiency/proofreading
180
Termination (Translation)
Triggered by stop codon-recognized by release factors; peptide chain released from ribosomal complex; catalyzes water and forms COOH end of polypeptide
181
Streptomycin
Binds to 30S subunit to disrupt initiation
182
Shiga toxin
Binds to 60S subunit to disrupt elongation
183
Clindamycin/erythromycin
Binds to 50s subunit to disrupt translocation of ribosome
184
Tetracyclines
Binds to 30S subunit to disrupt elongation
185
Puromycin
Can trick the cell into binding because it resembles aminoacylated 3' end of tyrosyl-tRNA; translation will stop
186
Polysomes
Clusters of ribosomes that attach to mRNA and make protein synthesis more efficient
187
Transport signal to mitochondria (cytoplasmic)
N-terminal hydrophobic alpha helix
188
Transport signal to nucleus (cytoplasmic)
Lys/Arg rich signals (KKKRK)
189
Transport signal to retention in ER (secretory)
Lys/Asp/Glu/Leu sequence (KDEL)
190
Transport signal to secretory vesicle (secretory)
Trp-rich domain
191
Transport signal to lysosome (secretory)
M6P
192
Transport signal to plasma membrane (secretory)
N-terminal apolar residues
193
TOM
Mitochondrial transporter on outer membrane
194
TIM
Mitochondrial transporter on inner membrane
195
Chaperones
Protect unfolded proteins during transport (HSP70)
196
SRP
Recognizes all particles in secretory pathway; attaches to ribosome and initiates translocation into ER
197
Chaperonins
Barrel shaped compartments, catalyze folding of proteins
198
Proteolytic cleavage
Converts inactive forms of enzymes to active forms
199
Glycosylation
Add sugar to protein; O-glycosidic linkage formed with -OH of Ser or Thr, N-glycosidic linkage formed with Asp
200
Phosphorylation
Formation of ester bond between phosphate and OH of AA via Ser/Thr and tyrosine kinase; regulates enzyme and protein activity
201
Disulfide bond formation
Form between SH group of 2 Cys in ER lumen
